Abstract
BackgroundThe BRAF K601E mutation occurs in 5% of patients with melanoma, and is the third most common type of BRAF mutation. However, treatment with BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is only approved in patients with BRAF V600-positive melanoma, and patients with K601E-mutated melanoma do not have access to such drugs.Case presentationA female patient was diagnosed with high tumor burden metastatic melanoma harboring the BRAF K601E mutation. After chemotherapy failure, she underwent compassionate treatment with trametinib. Trametinib showed good activity and efficacy, with 48% shrinkage of a metastatic lymphadenopathy after 4 months’ treatment. However, the patient reported treatment-related skin toxicity that required dosage reduction and a personalized intermittent trametinib dosing schedule. After over 36 months from the first trametinib administration, and resection of a metastatic lymphadenopathy, the patient experienced complete response.ConclusionsThis case report shows that trametinib could be a valid therapeutic option in patients with metastatic melanoma harboring the rare BRAF K601E mutation.
Highlights
The BRAF K601E mutation occurs in 5% of patients with melanoma, and is the third most common type of BRAF mutation
This case report shows that trametinib could be a valid therapeutic option in patients with metastatic melanoma harboring the rare BRAF K601E mutation
We describe a case report of a patient with BRAF K601Emutated melanoma who achieved complete response to the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib, that underlines a possible therapeutic option for these patients
Summary
Melanoma is the fourth most common malignancy in men and women. Efficacious targeted therapies such as BRAF and mitogen-activated extracellular signalregulated kinase (MEK) inhibitors are available for patients with melanoma harboring BRAF V600 mutations. Due to grade 1 asthenia, articular pain in the ankles, knees, and wrists, and the earlier grade 3 skin toxicities, the patient received symptomatic treatment and the schedule of trametinib therapy was modified to an on/ off regimen: 2 weeks of trametinib 1 mg/day, followed by 1 week of no trametinib administration. With this new schedule, the patient experienced no adverse effects and was able to continue treatment with trametinib. The patient continues to receive trametinib with a personalized on/off schedule
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